Title

Author

Document Type

Dissertation

Date of Degree

Fall 2014

Degree Name

PhD (Doctor of Philosophy)

Degree In

Health Management and Policy

First Advisor

George L. Wehby

Abstract

Neural tube defects (NTD) are among the most common birth defects and the leading cause of infant mortality. NTDs occur when the neural tube fails to close during early fetal development. The two most common types of NTD are spina bifida and anencephaly. NTDs result in lifelong complications like musculoskeletal deformities and loss of strength. The etiology of NTDs is complex and involves still unclear environmental and genetic factors. However, one of the well-established risk factors of NTDs is folic acid deficiency. The prevalence of NTDs can be lowered by an adequate intake of folic acid in the periconceptual period. In 1996, the Food and Drug Administration mandated that 140 micrograms of folic acid be added to 100 grams of bleached grain products with the goal of reducing the prevalence of NTDs. In the years following this fortification mandate, studies have shown that blood folate levels have more than doubled on average, that there are demographic and socioeconomic disparities in blood folate gains and that NTD rates have declined. However, no studies after the mandate have examined changes in blood folate distribution and differences in NTD prevalence by a wide range of theoretically and biologically relevant risk factors after the mandate.

Using a nationally representative sample of non-institutionalized women of reproductive age, I investigated the relationship between the fortification mandate and blood folate levels. I also examined changes in the range/spread of blood folate distribution after the mandate. Using data on US live births from 45 states and the District of Colombia, the second study examined whether (1) the disparities in blood folate changes translate into differences in NTD prevalence and (2) NTD risk factors moderate the association between the mandate and NTD prevalence,. The final study explored potential unintended impacts of the mandate on birth weight, low birth weight, very low birth weight, high birth weight, and physician-diagnosed developmental delay, asthma and allergies. For this study, I employed samples from the Natality files and the National Survey for Children's Health.

The cumulative results of my research suggested that the mandate was associated with increases in blood folate concentration, with greater increases in higher quantiles of the blood folate distribution and that the spread of blood folate distribution after the mandate widened. Additionally, the mandate was associated with a decrease in the prevalence of NTDs in the entire US population although the impact of the mandate was moderated by race/ethnicity, maternal educational attainment, acute illness during pregnancy and infant region of birth. Furthermore, the mandate was associated with other unintended infant and child health outcomes such as average birth weight increases in the population and increased risks of developmental delay among six year olds.

This research is the first of its kind to examine changes in the spread of blood folate distribution after the mandate and whether NTD risk factors moderate the association between the mandate and NTD prevalence. It is also the first study to explore potential impacts of the actual mandate (not prenatal folic acid supplementation) on other unintended infant and child health outcomes. The results add significantly to our understanding of the effects of the mandate and have important implications for health care providers, women of reproductive age and policy makers because of the potentially increased risk of developmental delay among children and the increasing disparity in blood folate concentrations after the mandate.